Landmark HI-PEITHO Trial Kicks Off 'Golden Era' in Pulmonary Embolism Treatment

Ultrasound-facilitated, catheter-directed thrombolysis significantly reduced cardiorespiratory decompensation in intermediate-risk PE patients compared to anticoagulation alone.

Mar. 28, 2026 at 8:05pm

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The HI-PEITHO trial, published simultaneously in the New England Journal of Medicine, found that ultrasound-facilitated, catheter-directed thrombolysis (CDT) using the EKOS+ endovascular device significantly reduced the composite endpoint of PE-related death, cardiorespiratory decompensation or collapse, and symptomatic PE recurrence within 7 days compared to anticoagulation alone in intermediate-risk pulmonary embolism (PE) patients. The benefit appeared to be driven by a reduction in cardiorespiratory decompensation, with similar safety profiles between the CDT and control groups.

Why it matters

HI-PEITHO is considered a landmark trial that could usher in a 'golden era' for PE treatment. For years, clinicians have hypothesized that delivering thrombolytics locally via catheter could maintain efficacy while reducing bleeding complications compared to systemic thrombolysis. This trial provides the first robust evidence supporting this approach in intermediate-risk PE patients, a difficult-to-treat group that has lacked clear guidance.

The details

HI-PEITHO screened 544 intermediate-risk PE patients in the U.S. and Europe from 2021-2025, randomizing them to anticoagulation with or without ultrasound-facilitated CDT using alteplase delivered via the EKOS+ device. The intervention group received an average total alteplase dose of 8.9 mg (for single-sided catheter placement) or 16.9 mg (for bilateral placement), with a mean infusion duration of 7.2 hours. The primary composite endpoint significantly favored the CDT group (4.0% vs 10.3%), driven by a reduction in cardiorespiratory decompensation or collapse. Safety outcomes like major bleeding were similar between groups.

  • HI-PEITHO screened patients from 2021 to 2025.
  • The trial results were presented at the American College of Cardiology (ACC) annual meeting in March 2026 and published simultaneously in the New England Journal of Medicine.

The players

Stavros Konstantinides, MD

Researcher at University Medical Center Mainz in Germany and lead investigator of the HI-PEITHO trial.

Jay Giri, MD, MPH

Cardiologist at the University of Pennsylvania who commented on the significance of the HI-PEITHO trial.

Mark Creager, MD

Cardiologist at Dartmouth-Hitchcock Medical Center who explained the clinical implications of the HI-PEITHO findings.

Lauren Westafer, DO, MPH

Emergency medicine physician at UMass Chan Medical School-Baystate who raised some caveats about the HI-PEITHO trial design and outcomes.

EKOS+

An endovascular device used to deliver ultrasound-facilitated, catheter-directed thrombolysis in the HI-PEITHO trial.

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What they’re saying

“I think it's a really big day for the field of RCTs [randomized clinical trials] and PE. For 15 years, we've had a hypothesis that by delivering the lytic locally, with much lower doses, we could sustain efficacy, but decrease complications, risks of bleeding.”

— Jay Giri, Cardiologist, University of Pennsylvania

“[HI-PEITHO is] a very exciting trial, I'd say the most important trial in hospitalized patients with PE in the last 12 years since the original PEITHO trial.”

— Jay Giri, Cardiologist, University of Pennsylvania

“Prior to [HI-PEITHO], there was insufficient data to support CDT for this group and clinicians were left to their best judgement on how to intervene. Clinicians would be more inclined to use advanced measures in [high-risk patients], since these patients are already showing signs of cardiopulmonary insufficiency or collapse.”

— Mark Creager, Cardiologist, Dartmouth-Hitchcock Medical Center

What’s next

Ongoing catheter-directed thrombolysis trials in intermediate-risk PE, such as PRAGUE-26 and PE-TRACT, as well as the mechanical thrombectomy trial PEERLESS II, are expected to further build on the findings of HI-PEITHO and solidify the role of advanced interventions in this patient population.

The takeaway

The HI-PEITHO trial represents a major breakthrough in the treatment of intermediate-risk pulmonary embolism, demonstrating that ultrasound-facilitated, catheter-directed thrombolysis can significantly reduce the risk of cardiorespiratory decompensation compared to anticoagulation alone, without increasing major bleeding complications. This trial is expected to usher in a 'golden era' of PE research and treatment, with several follow-up studies already underway.